Aging may be less about specific “aging genes” and more about how long a gene is, according to a recent opinion piece in Trends in Genetics. Researchers from four different groups suggest that many changes associated with aging could be due to decreased expression of long genes. This decline in expression has been observed across various animals and in individuals with neurodegenerative diseases.
“If you ask me, this is the main cause of systemic aging in the whole body,” says co-author and molecular biologist Jan Hoeijmakers of the Erasmus University Medical Center, Rotterdam.
The study highlights that aging is linked to changes at molecular, cellular, and organ levels, stemming from DNA damage caused by factors like UV radiation and reactive oxygen species. While past research focused on specific aging-related genes, recent findings indicate that susceptibility to aging is more related to gene length than function.
“For a long time, the aging field has been focused on genes associated with aging, but our explanation is that it is much more random—it’s a physical phenomenon related to the length of the genes and not to the specific genes involved or the function of those genes,” adds co-author Ander Izeta of the Biogipuzkoa Health Research Institute.
Long genes are more prone to damage due to their size, akin to a longer road trip having more chances for mishaps. Cells expressing long genes, especially neural cells, are particularly vulnerable as they accumulate DNA damage over time. This vulnerability is associated with neurodegeneration and premature aging in certain cases.
The research also suggests that known anti-aging factors like dietary restriction can mitigate the decline in long-gene expression. While the link between gene length and aging is strong, further studies are needed to establish causation. Future research aims to delve deeper into the mechanisms and evolutionary implications of this phenomenon and its connection to neurodegeneration.